Reactive oxygen species (ROS) triggers unconventional secretion of antioxidants and Acb1

Abstract

Nutrient deprivation triggers the release of signal-sequence-lacking Acb1 and the antioxidant superoxide dismutase 1 (SOD1). We now report that secreted SOD1 is functionally active and accompanied by export of other antioxidant enzymes such as thioredoxins, (Trx1 and Trx2) and peroxiredoxin Ahp1, in a Grh1 dependent manner. Our data reveal that starvation leads to production of non-toxic levels of reactive oxygen species (ROS). Treatment of cells with N-acetylcysteine (NAC), which sequesters ROS, prevents antioxidants and Acb1 secretion. Starved cells lacking Grh1 are metabolically active, but defective in their ability to regrow upon return to growth conditions. Treatment with NAC restored the Grh1 dependent effect of starvation on cell growth. In sum, starvation triggers ROS production and cells respond by secreting antioxidants and Acb1, which is an important lipogenic signaling molecule in mammalian cells. We suggest that unconventional secretion of antioxidants and Acb1 like activities maintains cells in a form necessary for growth upon their eventual return from starvation to normal conditions.